Parasite stress theory has recently been used to account for an array of cross-cultural differences in human cognition and social behavior, including in-group bias, interpersonal violence, child maltreatment, and religious adherence. Here, we re-assess the apparently ubiquitous effects of parasite stress on behavior observed in the U.S., using the cross-sectional, cross-population approach implemented by prior pathogen stress studies. Our results raise two challenges to previous findings. First, we show that the observed effects of pathogen stress in the U.S. data are due exclusively to one type of infectious disease – sexually transmitted diseases (STD) – while non-STD infections have no effect. Second, we find that controlling for life history measures of extrinsic risk and a fast life history erases the observed associations with family ties, interpersonal violence, child fatalities, and religious adherence. Thus, after appropriate variable specification, stratification, and control, U.S. cross-state population differences provide no support for the pathogen stress hypothesis in these various domains of behavior. Rather, the findings are more consistent with predictions from life history theory.